tbuckley/cabot-search huggingface dataset:
Photoactive intragastric satiety-inducing device using polymeric photosensitizers for minimally invasive weight loss treatment
Authors: Ji Won Kim, Sanghee Lee, Dae Sung Ryu, Jinhwan Park, Hyeonseung Lee, Hee Kyong Na, Jin Hee Noh, Do Hoon Kim, Jung-Hoon Park, Hwoon-Yong Jung, Kun Na
Journal: Biomaterials (2023)
Mortality Risk of Hot Nights: A Nationwide Population-Based Retrospective Study in Japan
Authors: Satbyul Estella Kim, Masahiro Hashizume, Ben Armstrong, Antonio Gasparrini, Kazutaka Oka, Yasuaki Hijioka, Ana M. Vicedo-Cabrera, Yasushi Honda
Journal: Environmental Health Perspectives (2023)

BACKGROUND:The health effects of heat are well documented; however, limited information is available regarding the health risks of hot nights.Hot nights have become more common, increasing at a faster rate than hot days, making it urgent to understand the characteristics of the hot night risk.OBJECTIVES: We estimated the effects of hot nights on the cause-and location-specific mortality in a nationwide assessment over 43 y (1973-2015) using a unified analytical framework in the 47 prefectures of Japan.METHODS: Hot nights were defined as days with a) minimum temperature ≥25 C (HN 25 ) and b) minimum temperature ≥95th percentile (HN 95th ) for the prefecture.We conducted a time-series analysis using a two-stage approach during the hot night occurrence season (April-November).For each prefecture, we estimated associations between hot nights and mortality controlling for potential confounders including daily mean temperature.We then used a random-effects meta-analytic model to estimate the pooled cumulative association.RESULTS: Overall, 24,721,226 deaths were included in this study.Nationally, all-cause mortality increased by 9%-10% [HN 25 relative risk ðRRÞ = 1:09, 95% confidence interval (CI): 1.08, 1.10; HN 95th RR = 1:10, 95% CI: 1.09, 1.11] during hot nights in comparison with nonhot nights.All 11 cause-specific mortalities were strongly associated with hot nights, and the corresponding associations appeared to be acute and lasted a few weeks, depending on the cause of death.The strength of the association between hot nights and mortality varied among prefectures.We found a higher mortality risk from hot nights in early summer in comparison with the late summer in all regions.CONCLUSIONS: Our findings support the evidence of mortality impacts from hot nights in excess of that explicable by daily mean temperature and have implications useful for establishing public health policy and research efforts estimating the health effects of climate change.
Paralog-specific signaling by IRAK1/4 maintains MyD88-independent functions in MDS/AML
Authors: Joshua Bennett, Chiharu Ishikawa, Puneet Agarwal, Jennifer Yeung, Avery Sampson, Emma Uible, Eric Vick, Lyndsey C. Bolanos, Kathleen Hueneman, Mark Wunderlich, Amal Kolt, Kwangmin Choi, Andrew Volk, Kenneth D. Greis, Jan Rosenbaum, Scott B. Hoyt, Craig J. Thomas, Daniel T. Starczynowski
Journal: Blood (2023)

Dysregulation of innate immune signaling is a hallmark of hematologic malignancies. Recent therapeutic efforts to subvert aberrant innate immune signaling in myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) have focused on the kinase IRAK4. IRAK4 inhibitors have achieved promising, though moderate, responses in preclinical studies and clinical trials for MDS and AML. The reasons underlying the limited responses to IRAK4 inhibitors remain unknown. In this study, we reveal that inhibiting IRAK4 in leukemic cells elicits functional complementation and compensation by its paralog, IRAK1. Using genetic approaches, we demonstrate that cotargeting IRAK1 and IRAK4 is required to suppress leukemic stem/progenitor cell (LSPC) function and induce differentiation in cell lines and patient-derived cells. Although IRAK1 and IRAK4 are presumed to function primarily downstream of the proximal adapter MyD88, we found that complementary and compensatory IRAK1 and IRAK4 dependencies in MDS/AML occur via noncanonical MyD88-independent pathways. Genomic and proteomic analyses revealed that IRAK1 and IRAK4 preserve the undifferentiated state of MDS/AML LSPCs by coordinating a network of pathways, including ones that converge on the polycomb repressive complex 2 complex and JAK-STAT signaling. To translate these findings, we implemented a structure-based design of a potent and selective dual IRAK1 and IRAK4 inhibitor KME-2780. MDS/AML cell lines and patient-derived samples showed significant suppression of LSPCs in xenograft and in vitro studies when treated with KME-2780 as compared with selective IRAK4 inhibitors. Our results provide a mechanistic basis and rationale for cotargeting IRAK1 and IRAK4 for the treatment of cancers, including MDS/AML.
Long-Term Outcomes of TROG 13.01 SAFRON II Randomized Trial of Single- Versus Multifraction Stereotactic Ablative Body Radiotherapy for Pulmonary Oligometastases
Authors: Shankar Siva, Pitchaya Sakyanun, Tao Mai, Wenchang Wong, Adeline Lim, Joanna Ludbrook, Catherine Bettington, Angela Rezo, David Pryor, Nicholas Hardcastle, Tomas Kron, Braden Higgs, Hien Le, Marketa Skala, Suki Gill, Thomas Eade, Raef Awad, Giuseppe Sasso, Shalini Vinod, Rebecca Montgomery, David Ball, Mathias Bressel
Journal: Journal of Clinical Oncology (2023)

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO or elsewhere, for which the primary end point has already been reported.In a randomized phase II clinical trial, the Trans Tasman Radiation Oncology Group compared single- versus multifraction stereotactic ablative body radiotherapy (SABR) in 90 patients with 133 oligometastases to the lung. The study found no differences in safety, efficacy, systemic immunogenicity, or survival between arms, with single-fraction SABR picked as the winner on the basis of cost-effectiveness. In this article, we report the final updated survival outcome analysis. The protocol mandated no concurrent or post-therapy systemic therapy until progression. Modified disease-free survival (mDFS) was defined as any progression not addressable by local therapy, or death. At a median follow-up of 5.4 years, the 3- and 5-year estimates for overall survival (OS) were 70% (95% CI, 59 to 78) and 51% (95% CI, 39 to 61). There were no significant differences between the multi- and single-fraction arms for OS (hazard ratio [HR], 1.1 [95% CI, 0.6 to 2.0]; P = .81). The 3- and 5-year estimates for disease-free survival were 24% (95% CI, 16 to 33) and 20% (95% CI, 13 to 29), with no differences between arms (HR, 1.0 [95% CI, 0.6 to 1.6]; P = .92). The 3- and 5-year estimates for mDFS were 39% (95% CI, 29 to 49) and 34% (95% CI, 24 to 44), with no differences between arms (HR, 1.0 [95% CI, 0.6 to 1.8]; P = .90). In this patient population, where patients receive SABR in lieu of systemic therapy, one-in-three patients are alive without disease in the long term. There were no differences in outcomes by fractionation schedule.
A Nomogram Predicting 10-Year Life Expectancy in Candidates for Radical Prostatectomy or Radiotherapy for Prostate Cancer
Authors: Jochen Walz, Andrea Gallina, Fred Saad, Francesco Montorsi, Paul Perrotte, Shahrokh F. Shariat, Claudio Jeldres, Markus Graefen, Francois Bénard, Michael McCormack, Luc Valiquette, Pierre I. Karakiewicz
Journal: Journal of Clinical Oncology (2007)

Purpose Candidates for definitive therapy for localized prostate cancer (PCa) should have life expectancy (LE) in excess of 10 years. However, LE estimation is difficult. To circumvent this problem, we developed a nomogram predicting 10-year LE for patients treated with either radical prostatectomy (RP) or external-beam radiation therapy (EBRT) and compared it with an existing tool. Patients and Methods Between 1989 and 2000, 9,131 men were treated with either RP (n = 5,955) or EBRT (n = 3,176), without any secondary therapy and all deaths were considered unrelated to PCa. Age and Charlson comorbidity index (CCI) predicted 10-year LE in Cox regression models. We used 200 bootstrap resamples to internally validate the nomogram. Results Median age was 66 years, median CCI was 1, median follow-up was 5.9 years and median actuarial survival was 13.8 years. Advanced age (P &lt; .001), elevated CCI score (P &lt; .001) and treatment type (EBRT v RP, P &lt; .001) were independent predictors of poor 10 year LE. The nomogram predicting 10 year LE after either RP or EBRT was 84.3% accurate in split sample validation and was 2.9% (P = .007) more accurate than the existing tool. A cutoff of 70% or less was 84% accurate in identifying men who did not survive beyond 10 years. Conclusion Our nomogram can accurately identify those individuals who do not have sufficient LE to warrant definitive PCa treatment and can help optimizing therapy decision-making.
Population Strategies to Decrease Sodium Intake and the Burden of Cardiovascular Disease
Authors: Crystal M. Smith-Spangler
Journal: Annals of Internal Medicine (2010)

Background: Sodium consumption raises blood pressure, increasing the risk for heart attack and stroke. Several countries, including the United States, are considering strategies to decrease population sodium intake. Objective: To assess the cost-effectiveness of 2 population strategies to reduce sodium intake: government collaboration with food manufacturers to voluntarily cut sodium in processed foods, modeled on the United Kingdom experience, and a sodium tax. Design: A Markov model was constructed with 4 health states: well, acute myocardial infarction (MI), acute stroke, and history of MI or stroke. Data Sources: Medical Panel Expenditure Survey (2006), Framingham Heart Study (1980 to 2003), Dietary Approaches to Stop Hypertension trial, and other published data. Target Population: U.S. adults aged 40 to 85 years. Time Horizon: Lifetime. Perspective: Societal. Outcome Measures: Incremental costs (2008 U.S. dollars), quality-adjusted life-years (QALYs), and MIs and strokes averted. Results of Base-Case Analysis: Collaboration with industry that decreases mean population sodium intake by 9.5% averts 513 885 strokes and 480 358 MIs over the lifetime of adults aged 40 to 85 years who are alive today compared with the status quo, increasing QALYs by 2.1 million and saving $32.1 billion in medical costs. A tax on sodium that decreases population sodium intake by 6% increases QALYs by 1.3 million and saves $22.4 billion over the same period. Results of Sensitivity Analysis: Results are sensitive to the assumption that consumers have no disutility with modest reductions in sodium intake. Limitation: Efforts to reduce population sodium intake could result in other dietary changes that are difficult to predict. Conclusion: Strategies to reduce sodium intake on a population level in the United States are likely to substantially reduce stroke and MI incidence, which would save billions of dollars in medical expenses. Primary Funding Source: Department of Veterans Affairs, Stanford University, and National Science Foundation.
Measles, Mumps, Rubella Vaccination and Autism
Authors: Anders Hviid, Jørgen Vinsløv Hansen, Morten Frisch, Mads Melbye
Journal: Annals of Internal Medicine (2019)

Background: The hypothesized link between the measles, mumps, rubella (MMR) vaccine and autism continues to cause concern and challenge vaccine uptake. Objective: To evaluate whether the MMR vaccine increases the risk for autism in children, subgroups of children, or time periods after vaccination. Design: Nationwide cohort study. Setting: Denmark. Participants: 657 461 children born in Denmark from 1999 through 31 December 2010, with follow-up from 1 year of age and through 31 August 2013. Measurements: Danish population registries were used to link information on MMR vaccination, autism diagnoses, other childhood vaccines, sibling history of autism, and autism risk factors to children in the cohort. Survival analysis of the time to autism diagnosis with Cox proportional hazards regression was used to estimate hazard ratios of autism according to MMR vaccination status, with adjustment for age, birth year, sex, other childhood vaccines, sibling history of autism, and autism risk factors (based on a disease risk score). Results: During 5 025 754 person-years of follow-up, 6517 children were diagnosed with autism (incidence rate, 129.7 per 100 000 person-years). Comparing MMR-vaccinated with MMR-unvaccinated children yielded a fully adjusted autism hazard ratio of 0.93 (95% CI, 0.85 to 1.02). Similarly, no increased risk for autism after MMR vaccination was consistently observed in subgroups of children defined according to sibling history of autism, autism risk factors (based on a disease risk score) or other childhood vaccinations, or during specified time periods after vaccination. Limitation: No individual medical charts were reviewed. Conclusion: The study strongly supports that MMR vaccination does not increase the risk for autism, does not trigger autism in susceptible children, and is not associated with clustering of autism cases after vaccination. It adds to previous studies through significant additional statistical power and by addressing hypotheses of susceptible subgroups and clustering of cases. Primary Funding Source: Novo Nordisk Foundation and Danish Ministry of Health.
Metachronous Hormonal Syndromes in Patients With Pancreatic Neuroendocrine Tumors
Authors: Louis de Mestier, Olivia Hentic, Jérôme Cros, Thomas Walter, Guillaume Roquin, Hedia Brixi, Catherine Lombard-Bohas, Pascal Hammel, Marie-Danièle Diebold, Anne Couvelard, Philippe Ruszniewski, Guillaume Cadiot
Journal: Annals of Internal Medicine (2015)

Background: Pancreatic neuroendocrine tumors (PNETs) may evolve and cause hormonal hypersecretion–related symptoms that were not present at the initial diagnosis, termed metachronous hormonal syndromes (MHSs). Their setting, characteristics, and outcomes are not well-described. Objective: To describe MHSs in patients with sporadic PNETs. Design: Retrospective, multicenter study. Setting: 4 French referral centers. Patients: Patients with PNETs who developed MHSs related to hypersecretion of insulin, gastrin, vasoactive intestinal peptide, or glucagon between January 2009 and January 2014. Measurements: Tumor extension, biological markers, and treatments at initial PNET diagnosis and MHS onset. Pathologic specimens were evaluated centrally, including Ki-67 index and hormone immunolabeling. Results: Of 435 patients with PNETs, 15 (3.4%) were identified as having MHSs involving the hypersecretion of insulin (5 patients), vasoactive intestinal peptide (5 patients), gastrin (2 patients), or glucagon (4 patients). Metachronous hormonal syndromes developed after a median of 55 months (range, 7 to 219) and in the context of PNET progression, stability, and tumor response in 8, 6, and 1 patients, respectively. The median Ki-67 index was 7% (range, 1% to 19%) at PNET diagnosis and 17.5% (range, 2.0% to 70.0%) at MHS onset. Immunolabeling of MHS-related peptides was retrospectively found in 8 of 14 of pathologic PNET specimens obtained before MHS diagnosis. Median survival after MHS onset was 28 months (range, 3 to 56). Seven patients with MHSs died during follow-up, all due to PNETs, including 4 patients with insulin-related MHSs. Limitation: Retrospective data collection and heterogeneity of pathologic specimen size and origin. Conclusion: Metachronous hormonal syndromes were identified more often in the context of PNET progression and increased Ki-67 indices. Patients with insulin-related MHSs may have decreased survival rates. Primary Funding Source: None.
Biologic Effects of Transdermal Estradiol
Authors: Ryszard J. Chetkowski, David R. Meldrum, Kenneth A. Steingold, Denise Randle, John K. Lu, Peter Eggena, Jerome M. Hershman, Norma K. Alkjaersig, Anthony P. Fletcher, Howard L. Judd
Journal: New England Journal of Medicine (1986)

We conducted a dose–response study in 23 postmenopausal women to compare the physiologic effects of transdermal estradiol and oral conjugated equine estrogens. The doses studied were 25, 50, 100, and 200 μg of transdermal estradiol per 24 hours, and 0.625 and 1.25 μg of oral conjugated estrogens. Transdermal estradiol increased circulating concentrations of estradiol and estrone. Oral conjugated estrogens also raised the levels of estrogen, particularly estrone. Both preparations lowered gonadotropin levels, decreased the percentages of vaginal parabasal cells, increased the percentage of superficial cells, and lowered urinary calcium excretion. The effects of 0.625 and 1.25 mg of oral estrogens were similar to those of 50 and 100 μg of transdermal estradiol per 24 hours, respectively. Oral estrogens significantly increased circulating levels of renin substrate, sex-hormone–binding globulin, thyroxine-binding globulin, and cortisol-binding globulin; transdermal estradiol had no effect. The higher dose of oral estrogens had favorable effects on concentrations of low-density and high-density lipoproteins, but transdermal estradiol did not. Neither preparation affected any of the four clotting factors studied. These data indicate that transdermal estradiol can elicit many of the desirable actions of estrogen while avoiding the pharmacologic effects of oral estrogens on hepatic proteins. (N Engl J Med 1986; 314:1615–20.)
Impact of Psychometrically Defined Deficits of Executive Functioning in Adults With Attention Deficit Hyperactivity Disorder
Authors: Joseph Biederman, Carter Petty, Ronna Fried, Jessie Fontanella, Alysa E. Doyle, Larry J. Seidman, Stephen V. Faraone
Journal: American Journal of Psychiatry (2006)

Objective: The association between deficits in executive functioning and functional outcomes was examined among adults with attention deficit hyperactivity disorder (ADHD). Method: Subjects were adults who did (N=213) and did not (N=145) meet DSM-IV criteria for ADHD. The authors defined having deficits in executive functioning as having at least two measures of executive functioning with scores 1.5 standard deviations below those of matched comparison subjects. Results: Significantly more adults with ADHD had deficits of executive functioning than comparison subjects. Deficits of executive functioning were associated with lower academic achievement, irrespective of ADHD status. Subjects with ADHD with deficits of executive functioning had a significantly lower socioeconomic status and a significant functional morbidity beyond the diagnosis of ADHD alone. Conclusions: Psychometrically defined deficits of executive functioning may help identify a subgroup of adults with ADHD at high risk for occupational and academic underachievement. More efforts are needed to identify cost-effective approaches to screen individuals with ADHD for deficits of executive functioning.
The Primary Prevention of Myocardial Infarction
Authors: JoAnn E. Manson, Heather Tosteson, Paul M. Ridker, Suzanne Satterfield, Patricia Hebert, Gerald T. O'Connor, Julie E. Buring, Charles H. Hennekens
Journal: New England Journal of Medicine (1992)

IN the United States, coronary heart disease — principally myocardial infarction — accounts for approximately 1 of every 3 deaths, or nearly 600,000 deaths each year.1 Almost 50 percent of the deaths attributed to myocardial infarction occur before the victims reach the hospital, and of the 500,000 people admitted each year for myocardial infarction, about 15 percent die during the hospitalization and another 7 to 10 percent die during the ensuing several years.2 , 3 A therapy for myocardial infarction that improved survival by even 20 percent would therefore affect tens of thousands of lives, and a similar benefit in the primary . . .
Reducing perinatal mortality.
Journal: BMJ (1979)

Reducing perinatal mortalityThe dissolutions of Parliament has brought a halt to the inquiry into means ofreducinig perinatal and neonatal mortality that was being conducted by the Social Services Sub- Committee' of the Expenditure Committee of the House of Commons under the chairmanship of Mrs Renee Short.The committee's work was timely, since the last 12 months has
Interleukin-23–Expressing Bone Marrow–Derived Neural Stem-Like Cells Exhibit Antitumor Activity against Intracranial Glioma
Authors: Xiangpeng Yuan, Jinwei Hu, Maria L. Belladonna, Keith L. Black, John S. Yu
Journal: Cancer Research (2006)

Abstract Neural progenitor-like cells have been isolated from bone marrow and the cells have the ability of tracking intracranial tumor. However, the capacity of the cells to deliver molecules for activating immune response against intracranial tumor and the identity of cellular and molecular factors that are involved in such immune responses have yet to be elucidated. Here, we isolated neural stem-like cells from the bone marrow of adult mice. The isolated cells were capable of producing progenies of three lineages, neurons, astrocytes, and oligodendrocytes, in vitro and tracking glioma in vivo. By genetically manipulating bone marrow–derived neural stem-like cells (BM-NSC) to express a recently discovered cytokine, interleukin (IL)-23, the cells showed protective effects in intracranial tumor-bearing C57BL/6 mice. Depletion of subpopulation lymphocytes showed that CD8+ T cells were critical for the antitumor immunity of IL-23–expressing BM-NSCs and that CD4+ T cells and natural killer (NK) cells participated in the activity. Furthermore, the IL-23–expressing BM-NSC-treated survivors were resistant to the same tumor rechallenge associated with enhanced IFN-γ, but not IL-17, expression in the brain tissue. Taken together, these data suggest that IL-23–expressing BM-NSCs can effectively induce antitumor immunity against intracranial gliomas. CD8+ T cells are critical for such antitumor activity; in addition, CD4+ T cells and NK cells are also involved. (Cancer Res 2006; 66(5): 2630-8)
Structure and Function of the Circulation.
Journal: Annals of Internal Medicine (1980)

This is the second in what will ultimately be a three volume treatise on applied aspects of the structure and function of blood vessels, and, as it appears from the present volume, lymphatic vessels.Although it suffers from some of the defects of the first volume, notably a somewhat haphazard placing of the different chapters, it is generally a much better piece of work.Following the pattern established in the first volume, the first chapter deals with historical aspects, in this instance, medieval and renaissance interpretations of the cardiovascular system.The rest of the first half of the book is taken up by chapters on the blood supply of the heart and lungs and of the brain.These are written to a much higher standard than many of the chapters on tissue and visceral blood supply in the preceding volume.The fact that they are followed by an authoritative account of lymphatics by F. C. Courtice, two short, but illuminating chapters on ageing and arterial structure and endothelial structure and ultrastructure by W. J. Cliff, and a reasoned and restrained discussion of the relationship between intimal cushions and atheroma by W. E. Stehbens also greatly enhances the value of the book.Indeed, if the standard set in this volume is maintained in the third, the series will go a long way towards achieving its aim of providing a comprehensive account of the structure and function of the circulation.A. D. HOYES
Adolescent idiopathic scoliosis.
Journal: BMJ (1979)

minutes.Those patients whose symptoms were relieved were offered treatment with carbamezapine in gradually increasing dosage until adequate concentrations were reached in about three weeks-usually 600-1000 mg daily.Patients who showed allergy or intolerance to carbamezapine were treated with diphenylhydantoin in doses up to 400 mg daily.This treatment proved successful, but after withdrawal of the drug the tinnitus slowly returned, so that it has to be given continuously with adequate monitoring of serum concentra- tions and toxic effects.